Tenofovir alafenamide fumarate

Drug Overview

TAF is a prodrug form of tenofovir, the active ingredient in Viread. Tenofovir mimics the natural
substrate of reverse transcriptase and is incorporated into nascent viral DNA strands during
replication. Once incorporated, tenofovir acts as a chain terminator and prevents further replication of
the viral genome (FDA.gov, 2013). TAF is in Phase III development in the US, Japan, and five major EU
markets (France, Germany, Italy, Spain, and the UK) for the treatment of chronic hepatitis B infection.

Analyst Outlook

Demonstrating an improved renal and bone safety profile over Viread (tenofovir disoproxil fumarate
[TDF]; Gilead/GlaxoSmithKline) will be paramount to tenofovir alafenamide fumarate’s (TAF’s; Gilead)
success in the future hepatitis B market. Gilead is developing TAF as a successor product to Viread in
the hope of protecting hepatitis B revenues from the threat of generic erosion. In order to promote
the swapping of patients from Viread, TAF must show convincing improvements in nephrotoxicity and
bone mineral density reductions in Phase III trials. Even if TAF is able to demonstrate a superior safety
profile, Datamonitor Healthcare expects that payer pressure to prescribe cheaper generics will greatly
hamper its penetration of first-line therapy, and will see its use reserved for patients with baseline
renal impairment and/or bone risk factors.